The purpose of the study was to determine whether either of two vaccines or prior infection would protect chimpanzees against a challenge previously shown to produce disease in human volunteers and in chimpanzees. The vaccines selected for the study were OSU-1A Formalin-inactivated vaccine and an acellular, protein-rich extract vaccine. All chimpanzees were challenged with 10 to the seventh CFU of M. pneumoniae strain PI-1428, a dose shown to produce disease in the earlier chimp study. Groups of three chimpanzees given a two-dose "priming schedule" (intraperitoneal followed by intratracheal) of either vaccine prior to challenge were not protected against colonization. M. pneumoniae colonization of lung, trachea and oropharynx in animals receiving either vaccine or the broth control showed a similar course. In contrast, the two chimps which had recovered from prior disease were protected and did not become colonized in the oropharangeal or tracheal specimens. No obvious differences between the immunized chimpanzees and the control chimpanzees are apparent in the duration of colonization or peak titers of the tracheal or lung tissues. For the chimpanzees previously infected, no mycoplasmas could be recovered from the oropharynx and trachea during the course of the study. Thus, the previously infected but recovered chimpanzees were relatively protected against reinfection with M. pneumoniae. Two animals, immunized with extract, showed no signs of clinical disease during 10 week observation period. Five animals had essentially no disease of any duration. This group included two chimpanzees which had been immunized with the OSU vaccine, one chimpanzee immunized with extract, and one each of the animals which had a prior infection and the unimmunized, challenged control. Thus, chimpanzees immunized with the experimental extract vaccine show more protection than the other groups. A manuscript is being prepared for publication.